What resolves this contention: Astrocyte-derived complement C3 is a hallmark of…

What resolves this contention: Astrocyte-derived complement C3 is a hallmark of the neurotoxic A1 reactive state and is upregulated in AD, Parkinson's, and other neurodegenerative diseases; C3+ reactive astrocytes are abundant in human post-mortem tissue vs. Genetic deletion of C3 is neuroprotective in APP/PS1 mice—preventing cognitive decline and hippocampal neuron loss—despite increasing amyloid plaque burden, indicating complement-mediated neuroinflammation rather than amyloid itself drives neurodegeneration / A1 reactive astrocytes are abundant in human post-mortem tissue from Alzheimer's, Huntington's, Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis. / C3 deficiency protected aged APP/PS1 mice against cognitive decline despite increased amyloid plaque burden.